PROJECT SUMMARY ? MOLECULAR AND CELLULAR ONCOGENESIS The Molecular and Cellular Oncogenesis program (MCO) consists of nine members, all engaged in translational cancer research and utilizing a broad continuum of basic, translational and patient-oriented studies. The overarching goal is to bring together a multidisciplinary array of high-end technologies under a uniquely collaborative culture to improve cancer diagnosis, prognosis and treatment. Accordingly, MCO Program members merge unique expertise in basic and translational cancer biology with proteomics, functional genomics, bioinformatics and medicinal chemistry to provide impactful contributions on three flagship research themes: i) mechanisms of cancer growth control, ii) targeted cancer therapeutics, and iii) systems biology/cancer ??omics?. Over the past five years, the MCO Program has continued to function as a unique hub for collaborative cancer research at Wistar, leveraging extensive intra- and inter-programmatic collaborations, exceptional cancer-focus, broad utilization of Shared Resources and strong partnership with neighboring Institutions. Thematic faculty recruitment efforts during last Cancer Center Support Grant (CCSG) budget period has been transformative for the MCO Program, building ?critical mass? in strategically prioritized scientific areas of cancer metabolism and early-stage cancer drug discovery. Rated Outstanding to Exceptional at the 2013 CCSG renewal, the MCO Program currently receives $3.41 million in peer-reviewed, cancer- related funding (total funding, $4.63 million), with $3.05 million from the NCI, resulting in an exceptional cancer focus of 89%. In addition, $3.19 million out of $3.41 million (93%) of peer-reviewed, cancer-related funding is the product of internal and/or external collaborations. The MCO Program remains a nationally-recognized leader in the bench-to-bedside melanoma research continuum signature with large, multi-investigator disease- focused funding, including a Specialized Program of Research Excellence (SPORE, P50 CA174523), a program project grant (P01 CA114046) and a U-type grant (U54 CA224070). In terms of scholarly contributions, MCO Program members published 170 cancer-related, discovery articles during the last five years. Of these, 23.5% and 35.8% were the product of intra- or inter-programmatic collaborations, respectively, bringing the total collaborative publications of the Program from 36% in 2013 to more than 48% in 2018. In addition, MCO Program members continue to lead the education and training of the next generation of leaders in cancer research, leveraging a successful, long-running T32 training grant (CA009171). Building on this steady track record of achievements, the MCO Program is ideally poised to further expand its central role as a multidisciplinary innovator in basic and translational cancer research during the next CCSG budget cycle, expanding new thematic areas in biomarker discovery for early cancer diagnosis and novel experimental therapeutics targeting vulnerabilities in tumor metabolism.